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Anticancer Res. 2016 Oct;36(10):5205-5213.

Expression of the p53 Inhibitors MDM2 and MDM4 as Outcome Predictor in Muscle-invasive Bladder Cancer.

Author information

1
Department of Urology, University Medical Centre Mannheim, Mannheim, Germany maximilian.kriegmair@medma.uni-heidelberg.de.
2
Department of Urology, University Medical Centre Mannheim, Mannheim, Germany.
3
Stratifyer Molecular Pathology, Köln, Germany.
4
Institute of Pathology, University Medical Centre Mannheim, Mannheim, Germany.
5
Department of Urology, University of Regensburg, Regensburg, Germany.
6
Institute of Pathology, University Erlangen-Nuernberg, Erlangen, Germany.
7
Department of Urology, University of Ulm, Ulm, Germany.

Abstract

AIM:

To evaluate the prognostic role of the p53-upstream inhibitors MDM2, MDM4 and its splice variant MDM4-S in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC).

MATERIALS AND METHODS:

mRNA Expression levels of MDM2, MDM4 and MDM4-S were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) in 75 RC samples. Logistic regression analyses identified predictors of recurrence-free (RFS) and cancer-specific survival (CSS).

RESULTS:

High expression was found in 42% (MDM2), 27% (MDMD4) and 91% (MDM4-S) of tumor specimens. Increased MDM2 expression was significantly associated with higher tumor stage (p=0.05) and lymphovascular invasion (LVI) (p=0.041). In the univariate analysis, low MDM4 expression (hazard ratio (HR)=5.93; p=0.002; HR=3.00; p=0.047), but not MDM2 (HR=1.63; p=0.222; HR=1.59; p=0.27), were associated with RFS and CSS. In the multivariate analysis, the combination of low MDM4 and high MDM2 was significant for RFS and CSS (HR=14.9; p=0.001; HR=5.63; p=0.019).

CONCLUSION:

The combination of MDM2 and MDM4 expression is an independent predictor in patients undergoing RC for MIBC.

KEYWORDS:

HDMX; MDM2; bladder cancer; marker; prognosis

PMID:
27798881
DOI:
10.21873/anticanres.11091
[Indexed for MEDLINE]

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